A5061931206- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Connexins and lens biology
- Metabolomics and Mass Spectrometry Studies
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
- Advanced Proteomics Techniques and Applications
- Genetic Mapping and Diversity in Plants and Animals
- Cardiovascular Function and Risk Factors
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Viral Infections and Immunology Research
- Cardiac pacing and defibrillation studies
- Chronic Lymphocytic Leukemia Research
- Congenital heart defects research
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Genomics and Rare Diseases
- Platelet Disorders and Treatments
- Adipose Tissue and Metabolism
- Atrial Fibrillation Management and Outcomes
Amsterdam University Medical Centers
2020-2022
Amsterdam UMC Location University of Amsterdam
2013-2020
University of Amsterdam
2013-2018
Montreal Heart Institute
2017
Université de Montréal
2017
Inserm
2017
Centre National de la Recherche Scientifique
2017
Sanquin
2013
Genome-wide association studies previously identified an of rs9388451 at chromosome 6q22.3 (near HEY2) with Brugada syndrome. The causal gene and underlying mechanism remain unresolved.We used integrative approach entailing transcriptomic in human hearts electrophysiological Hey2+/- (Hey2 heterozygous knockout) mice to dissect the underpinnings 6q22.31 syndrome.We queried expression quantitative trait locus data acquired 190 left ventricular samples from genotype-tissue consortium for...
Abstract Aims Cardiac arrhythmias comprise a major health and economic burden are associated with significant morbidity mortality, including cardiac failure, stroke, sudden death (SCD). Development of efficient preventive therapeutic strategies is hampered by incomplete knowledge disease mechanisms pathways. Our aim to identify novel underlying arrhythmia SCD using an unbiased approach. Methods results We employed phenotype-driven N-ethyl-N-nitrosourea mutagenesis screen identified mouse...
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Mutations in SCN5A, the gene encoding α-subunit of cardiac sodium channel (NaV1.5), are associated with a broad spectrum inherited arrhythmia disorders. The purpose this study was to identify genetic and functional determinants underlying Dutch family that presented combined phenotype ventricular arrhythmias likely adrenergic component, either isolation or combination mildly decreased heart function early onset (<55years) atrial fibrillation.We performed next generation sequencing proband...
Introduction: Disturbances in cardiac conduction contribute significantly to arrhythmia and sudden death the setting of common rare pathologies. The voltage-gated sodium channel (Nav1.5) is essential for normal conduction. This does not function isolation but interacts with other proteins which influence its expression modulate function. In-depth characterisation Nav1.5 macromolecular complex thus critical a full understanding Methods: We engineered protein A tag calmodulin binding peptide...
As part of a large-scale phenotype-driven screen we identified line exhibiting sudden death. Mapping and whole genome sequencing missense mutation in the Bcat2 gene, encoding mitochondrial branched chained aminotransferase, resulting an early stop (Q300*) truncated protein. Homozygous mice exhibited increased plasma urine levels chain amino acids (BCAAs). Mutations this pathway have previously been associated with Maple Syrup Urine Disease (MSUD) can result neurological symptoms. All...
Abstract Background In the past decade, we and others have reported three families with rare genetic variants in TNNI3K, encoding cardiac-specific troponin-I interacting kinase (TNNI3K), co-segregating a mixed, but highly penetrant, cardiac phenotype that features predominant atrial/junctional tachycardia occurring combination conduction disease dilated cardiomyopathy. We demonstrated while p.Thr539Ala p.Gly526Asp TNNI3K had decreased auto-phosphorylation activity p.Glu768Lys variant,...
Abstract Background Genome-wide association studies have associated a locus spanning GOSR2 with QRS- and QT-interval. encodes Membrin, protein located at the cis-Golgi, which plays role in trafficking. Altered trafficking of cardiac sodium channel (NaV1.5), encoded by SCN5A, has been shown to reduce conduction. Purpose To explore modulatory Membrin on conduction availability. Methods results Tandem Affinity Purification H10 cells (derived from neonatal rat cardiomyocytes) overexpressing...
Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main source(s): The Dutch Research Council (NWO Talent Scheme) Introduction Cardiac conduction delay is the main substrate for triggering arrhythmias. Hence, prolongation PR interval on electrocardiogram (ECG) a strong predictor atrial fibrillation, most common cardiac arrhythmia. In previous research, troponin I-interacting kinase (TNNI3K) has been identified as regulator interval. Various...